Cellular mechanisms of spatial navigation in the medial entorhinal cortex

Neurons in the medial entorhinal cortex exhibit a grid-like spatial pattern of spike rates that has been proposed to represent a neural code for path integration. To understand how grid cell firing arises from the combination of intrinsic conductances and synaptic input in medial entorhinal stellate cells, we performed patch-clamp recordings in mice navigating in a virtual-reality environment. We found that the membrane potential signature of stellate cells during firing field crossings consisted of a slow depolarization driving spike output. This was best predicted by network models in which neurons receive sustained depolarizing synaptic input during a field crossing, such as continuous attractor network models of grid cell firing. Another key feature of the data, phase precession of intracellular theta oscillations and spiking with respect to extracellular theta oscillations, was best captured by an oscillatory interference model. Thus, these findings provide crucial new information for a quantitative understanding of the cellular basis of spatial navigation in the entorhinal cortex.